DE69811844D1 - Thiazole Derivate - Google Patents
Thiazole DerivateInfo
- Publication number
- DE69811844D1 DE69811844D1 DE69811844T DE69811844T DE69811844D1 DE 69811844 D1 DE69811844 D1 DE 69811844D1 DE 69811844 T DE69811844 T DE 69811844T DE 69811844 T DE69811844 T DE 69811844T DE 69811844 D1 DE69811844 D1 DE 69811844D1
- Authority
- DE
- Germany
- Prior art keywords
- thiazole derivatives
- thiazole
- derivatives
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000007979 thiazole derivatives Chemical class 0.000 title 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1024—Tetrapeptides with the first amino acid being heterocyclic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Dermatology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98100006 | 1998-01-02 |
Publications (2)
Publication Number | Publication Date |
---|---|
DE69811844D1 true DE69811844D1 (de) | 2003-04-10 |
DE69811844T2 DE69811844T2 (de) | 2003-12-04 |
Family
ID=8231229
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69811844T Expired - Fee Related DE69811844T2 (de) | 1998-01-02 | 1998-12-24 | Thiazole Derivate |
Country Status (30)
Country | Link |
---|---|
US (3) | US6100282A (de) |
JP (1) | JP3113237B2 (de) |
KR (1) | KR100312901B1 (de) |
CN (1) | CN1080720C (de) |
AR (1) | AR014949A1 (de) |
AT (1) | ATE233746T1 (de) |
AU (1) | AU720618B2 (de) |
BR (1) | BR9900006A (de) |
CA (1) | CA2257328C (de) |
CO (1) | CO4990934A1 (de) |
DE (1) | DE69811844T2 (de) |
DK (1) | DK0928790T3 (de) |
ES (1) | ES2193471T3 (de) |
HK (1) | HK1020953A1 (de) |
HR (1) | HRP980645A2 (de) |
HU (1) | HUP9803040A3 (de) |
ID (1) | ID21936A (de) |
IL (1) | IL127785A (de) |
MA (1) | MA26591A1 (de) |
NO (1) | NO312067B1 (de) |
NZ (2) | NZ333590A (de) |
PE (1) | PE20000061A1 (de) |
PL (1) | PL330619A1 (de) |
PT (1) | PT928790E (de) |
RU (1) | RU2218337C2 (de) |
SG (1) | SG74686A1 (de) |
TR (1) | TR199802765A3 (de) |
UY (1) | UY25334A1 (de) |
YU (1) | YU61398A (de) |
ZA (1) | ZA9811925B (de) |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6919366B2 (en) * | 1998-05-22 | 2005-07-19 | Avanir Pharmaceuticals | Benzimidazole derivatives as modulators of IgE |
US6911462B2 (en) * | 1998-05-22 | 2005-06-28 | Avanir Pharmaceuticals | Benzimidazole compounds for regulating IgE |
GB9826174D0 (en) * | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
WO2001004103A1 (en) | 1999-07-13 | 2001-01-18 | F. Hoffmann-La Roche Ag | Benzazepinones and quinazolines |
US6759425B2 (en) * | 1999-10-21 | 2004-07-06 | Avanir Pharmaceuticals | Benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
JP2004501863A (ja) * | 2000-01-19 | 2004-01-22 | アルテオン インコーポレーテッド | チアゾール、イミダゾールおよびオキサゾール化合物、ならびにタンパク質老化関連疾患の治療 |
WO2002072090A1 (en) * | 2001-03-12 | 2002-09-19 | Avanir Pharmaceuticals | Benzimidazole compounds for modulating ige and inhibiting cellular proliferation |
TWI314928B (en) * | 2002-02-28 | 2009-09-21 | Novartis A | 5-phenylthiazole derivatives and use as pi3 kinase inhibitors |
TW200304820A (en) * | 2002-03-25 | 2003-10-16 | Avanir Pharmaceuticals | Use of benzimidazole analogs in the treatment of cell proliferation |
TWI276631B (en) * | 2002-09-12 | 2007-03-21 | Avanir Pharmaceuticals | Phenyl-aza-benzimidazole compounds for modulating IgE and inhibiting cellular proliferation |
AU2003270426A1 (en) | 2002-09-12 | 2004-04-30 | Avanir Pharmaceuticals | PHENYL-INDOLE COMPOUNDS FOR MODULATING IgE AND INHIBITING CELLULAR PROLIFERATION |
WO2005013950A2 (en) * | 2003-08-08 | 2005-02-17 | Avanir Pharmaceuticals | Selective pharmacologic inhibition of protein trafficking and related methods of treating human diseases |
US7652146B2 (en) * | 2004-02-06 | 2010-01-26 | Bristol-Myers Squibb Company | Process for preparing 2-aminothiazole-5-carboxamides useful as kinase inhibitors |
CN101031567B (zh) * | 2004-09-20 | 2011-12-21 | 4Sc股份有限公司 | 新型杂环NF-κB抑制剂 |
US8716320B2 (en) * | 2006-07-21 | 2014-05-06 | Replidyne, Inc. | Antibacteriall heterocyclic ureas |
JP5412429B2 (ja) | 2007-07-23 | 2014-02-12 | クレストーン・インコーポレーテッド | 抗細菌性アミド及びスルホンアミド置換複素環式尿素化合物 |
WO2009015193A1 (en) * | 2007-07-23 | 2009-01-29 | Replidyne, Inc. | Antibacterial sulfone and sulfoxide substituted heterocyclic urea compounds |
TWI504598B (zh) * | 2009-03-20 | 2015-10-21 | Onyx Therapeutics Inc | 結晶性三肽環氧酮蛋白酶抑制劑 |
CN102936257B (zh) * | 2012-08-30 | 2016-03-30 | 齐鲁工业大学 | 一类含银的噻唑西弗碱配合物的结构、制备和用途 |
EP3645531A1 (de) | 2017-06-29 | 2020-05-06 | Bayer Aktiengesellschaft | Thiazolverbindungen als prmt5-inhibitoren |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2009155B (en) * | 1977-11-07 | 1982-07-21 | Leo Pharm Prod Ltd | Chemical compounds |
FR2581063B1 (fr) * | 1985-04-30 | 1987-07-17 | Chauvin Blache Lab | Amino-2 thiazoles n-substitues, leur procede de preparation et leur application en therapeutique |
JPS62123180A (ja) * | 1985-11-21 | 1987-06-04 | Otsuka Pharmaceut Factory Inc | p−アミノフエノ−ル誘導体 |
US5000775A (en) * | 1985-12-31 | 1991-03-19 | Monsanto Company | 2-amino-4,5-disubstituted-oxazole/thiazole compounds as herbicide antidotes |
JPS6348873A (ja) * | 1986-08-19 | 1988-03-01 | Toshiba Corp | ガスレ−ザ発振装置 |
CA2037153A1 (en) * | 1990-03-09 | 1991-09-10 | Leo Alig | Acetic acid derivatives |
US5273982A (en) * | 1990-03-09 | 1993-12-28 | Hoffmann-La Roche Inc. | Acetic acid derivatives |
FI922867A (fi) * | 1991-06-21 | 1992-12-22 | Tanabe Seiyaku Co | Dikarbonsyraderivat och foerfarande foer framstaellning av dem |
US5294713A (en) * | 1991-08-23 | 1994-03-15 | Takeda Chemical Industries, Ltd. | 2-piperazinone compounds and their use |
GB9125970D0 (en) * | 1991-12-06 | 1992-02-05 | Fujisawa Pharmaceutical Co | New compounds |
US5514643A (en) * | 1993-08-16 | 1996-05-07 | Lucky Ltd. | 2-aminothiazolecarboxamide derivatives, processes for preparing the same and use thereof for controlling phytopathogenic organisms |
US6306840B1 (en) * | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
JPH08337579A (ja) * | 1995-06-14 | 1996-12-24 | Fujisawa Pharmaceut Co Ltd | グアニジノチアゾ−ルおよびその抗潰瘍剤、h2−受容体拮抗剤および抗菌剤としての用途 |
JPH09295974A (ja) * | 1995-09-11 | 1997-11-18 | Nippon Nohyaku Co Ltd | アゾール誘導体、その用途及びその製造方法並びにその使用方法 |
AU679887B2 (en) * | 1995-09-11 | 1997-07-10 | Nihon Nohyaku Co., Ltd. | Azole derivatives, their use, production and usage |
DK0871619T3 (da) * | 1995-12-29 | 2003-03-03 | Boehringer Ingelheim Pharma | Phenylthiazolderivater med antiherpesvirusegenskaber |
MA26487A1 (fr) * | 1997-04-29 | 2004-12-20 | Smithkline Beecham Corp | Heterocyclecetohydrazides inhibiteurs de proteases, procede pour leur preparation et compositions pharmaceutiques les contenant . |
-
1998
- 1998-12-22 US US09/218,567 patent/US6100282A/en not_active Expired - Fee Related
- 1998-12-24 DE DE69811844T patent/DE69811844T2/de not_active Expired - Fee Related
- 1998-12-24 NZ NZ333590A patent/NZ333590A/xx unknown
- 1998-12-24 NZ NZ333591A patent/NZ333591A/xx unknown
- 1998-12-24 DK DK98124670T patent/DK0928790T3/da active
- 1998-12-24 AT AT98124670T patent/ATE233746T1/de not_active IP Right Cessation
- 1998-12-24 PT PT98124670T patent/PT928790E/pt unknown
- 1998-12-24 ES ES98124670T patent/ES2193471T3/es not_active Expired - Lifetime
- 1998-12-28 NO NO19986159A patent/NO312067B1/no unknown
- 1998-12-29 PE PE1998001293A patent/PE20000061A1/es not_active Application Discontinuation
- 1998-12-29 ZA ZA9811925A patent/ZA9811925B/xx unknown
- 1998-12-29 HR HR98100006.0A patent/HRP980645A2/hr not_active Application Discontinuation
- 1998-12-29 IL IL12778598A patent/IL127785A/en not_active IP Right Cessation
- 1998-12-29 AR ARP980106723A patent/AR014949A1/es not_active Application Discontinuation
- 1998-12-30 HU HU9803040A patent/HUP9803040A3/hu unknown
- 1998-12-30 TR TR1998/02765A patent/TR199802765A3/tr unknown
- 1998-12-30 CO CO98077476A patent/CO4990934A1/es unknown
- 1998-12-30 PL PL98330619A patent/PL330619A1/xx not_active Application Discontinuation
- 1998-12-30 SG SG1998005978A patent/SG74686A1/en unknown
- 1998-12-30 CA CA002257328A patent/CA2257328C/en not_active Expired - Fee Related
- 1998-12-30 AU AU96144/98A patent/AU720618B2/en not_active Ceased
- 1998-12-30 MA MA25411A patent/MA26591A1/fr unknown
- 1998-12-30 YU YU61398A patent/YU61398A/sh unknown
- 1998-12-31 KR KR1019980063364A patent/KR100312901B1/ko not_active IP Right Cessation
- 1998-12-31 CN CN98125982A patent/CN1080720C/zh not_active Expired - Fee Related
- 1998-12-31 UY UY25334A patent/UY25334A1/es not_active IP Right Cessation
-
1999
- 1999-01-04 ID IDP990001D patent/ID21936A/id unknown
- 1999-01-04 BR BR9900006-7A patent/BR9900006A/pt not_active Application Discontinuation
- 1999-01-04 JP JP11000010A patent/JP3113237B2/ja not_active Expired - Fee Related
- 1999-01-05 RU RU99100277/04A patent/RU2218337C2/ru not_active IP Right Cessation
- 1999-12-28 HK HK99106136A patent/HK1020953A1/xx not_active IP Right Cessation
-
2000
- 2000-03-15 US US09/526,033 patent/US6320054B1/en not_active Expired - Fee Related
-
2001
- 2001-06-11 US US09/878,704 patent/US6344562B1/en not_active Expired - Fee Related
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
8364 | No opposition during term of opposition | ||
8339 | Ceased/non-payment of the annual fee |